Inhibition of BMP signaling reduces MMP-2 and MMP-9 expression and obstructs wound healing in regenerating fin of teleost fish Poecilia latipinna

Rajaram, Shailja; Murawala, Hiral; Buch, Pranav; Patel, Sonam; Balakrishnan, Suresh

doi:10.1007/s10695-015-0175-1

Cited by 20 publications

(22 citation statements)

References 45 publications

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“…However, among all the matrix metalloproteinases, MMP2 and MMP9 have been studied extensively for their role in ECM remodelling (Matrisian, ; Stamenkovic, ; Bonnans et al, ). In a recent study, it has been observed that inhibition of bone morphogenetic protein (BMP) signalling significantly decreased the expression of MMP2 and MMP9 in the wound epithelium stage of the regenerating caudal fin of P. latipinna, resulting in improper regeneration of the amputated organ (Rajaram et al, ). There are also reports that highlight the presence of MMPs in one or the other stages of epimorphosis (Santosh et al, ; Sharma et al, ; Rajaram et al, ).…”

Section: Discussionmentioning

confidence: 99%

Variation in expression and activity pattern ofmmp2andmmp9on different time scales in the regenerating caudal fin ofPoecilia latipinna

Murawala

Patel

Ranadive

et al. 2018

Journal of Fish Biology

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Alteration in the expression pattern of matrix metalloproteinase (MMP)2 and MMP9 was studied in the regenerating caudal fin of Poecilia latipinna immediately following amputation until the new tissues gained structural integrity. Timed expression pattern of these two MMPs was studied at enzyme, transcript as well as protein levels. Additionally, both the gelatinases were localized in the regenerating caudal fin during three specific stages of regeneration. The results revealed a progressive increase in the expression of MMP2 starting at 1 h post amputation (hpa), indicating its possible role in the remodelling of extracellular matrix early on during caudal-fin regeneration. Nevertheless, a reduction in transcript level expression of MMP2 at 6 hpa and 12 hpa stages, points towards a possible transcriptional regulation, to further moderate its activity. As observed in the case of MMP2, expression of MMP9 too increased from 1 hpa and remained elevated until 5 dpa. However, the active MMP9 revealed its presence only 12 hpa onwards. Moreover, both the gelatinases were localised in the apical epithelial cap and in the progress zone at wound epithelium (1 dpa) and blastema (60 hpa) stages respectively. Further, during early differentiation stage (5 dpa), high intensities of MMP2 and MMP9 were localized in the newly formed actinotrichia as compared with the tissue proximal to it. Based on the results, it could be construed that the controlled up-regulation of MMP2 and MMP9 from 1 hpa until the early differentiation stage ensures a regulated digestion of extracellular matrix, perhaps to facilitate the recruitment, proliferation, morphogenesis and re-patterning of resident stem cells during caudal fin regeneration in P. latipinna.

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Section: Discussionmentioning

confidence: 99%

Variation in expression and activity pattern ofmmp2andmmp9on different time scales in the regenerating caudal fin ofPoecilia latipinna

Murawala

Patel

Ranadive

et al. 2018

Journal of Fish Biology

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“…It is previously known that regeneration involves controlled expression of peptides and transcripts of signalling molecules at each stage of epimorphosis [18,19,31]. Therefore, to identify the stage-specific expression of peptides, we performed two dimensional gel electrophoresis.…”

Section: Discussionmentioning

confidence: 99%

Temporal Expression Pattern of Peptides in the Regenerating Caudal Fin of Teleost Fish Poecilia latipinna With Special Emphasis on krt15 and myl-1

Murawala¹,

Ranadive²,

Patel³

et al. 2017

Eur J Exp Bio

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Amongst several vertebrates, caudal fin of teleost fish has emerged as an excellent model to understand the mechanism of regeneration. By now it is well perceived that proper coordination of different regulatory signals are needed to facilitate the progression of successive stages of regeneration. Therefore, in the current study protein expression profile for caudal fin regeneration in Poecilia latipnna was brought into the focus. The pattern of protein turnover and variation in the expression level were observed across the stages of regeneration. Data from twodimensional gel electrophoresis revealed the differential expression of proteins for wound epithelium, blastema and differentiation stages when compared to resting stage. Based on the computational analysis, of the peptide expression profile and subsequent sequencing, two peptides namely Keratin type I cytoskeletal 15 and Myosin light chain-1 were studied further at transcript level. Keratin-15 was found to be up regulated at wound epithelium stage while its expression waned significantly in the blastema and differentiation stages of regeneration indicating its role in the formation of a functional wound epithelium. Western blot analysis of Keratin-15 also concurred with transcript levels of krt15. However, myl-1 transcript levels was observed to be dispensable for initial phase of regeneration whereas its elevated level in differentiation stage at both mRNA and protein level marks its noteworthy role in achieving the structural integrity of a regenerating caudal fin. This is the first observation of the involvement of Keratin-15 and Myosin light chain-1 in the regulation of regenerative process in Poecilia latipinna.

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“…[88][89][90] Inhibition of the BMP receptor and its downstream signaling by a pharmacological ligand significantly reduces the expression and activity of both MMP-2 and MMP-9, thereby obstructing tissue regeneration and remodeling in teleost fish Poecilia latipinna following amputation. 91 Similarly in mice with BMP type IA receptor (BMPRIA) deficiency specifically in osteoblasts, MMP-9 expressed by osteoclasts was significantly reduced, impairing bone resorption and finally resulting in increased bone mass during early development. 90 Additionally, Choi et al 92 reported that downregulation of MMP-9 activity promotes …”

Section: Bone Morphogenetic Proteinsmentioning

confidence: 99%

Matrix metalloproteinases in bone development and pathology: current knowledge and potential clinical utility

Liang¹,

Xu²,

Xue³

et al. 2016

MNM

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Matrix metalloproteinases (MMPs) are degrading enzymes that have a pivotal function in extracellular matrix remodeling. More than half of the MMP members are expressed by bone and cartilage cells under physiological or pathological conditions such as rheumatoid arthritis, osteoarthritis, and osteoporosis. Through studies on the various bone diseases and on genetically modified mouse models in which one or more of the MMPs or their associated proteins and downstream signaling molecules have been targeted, it is becoming increasingly evident that MMPs and other players in their cellular pathway play a pivotal role in bone development and remodeling. This review details the latest findings related to MMPs and bone development and pathology.

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Inhibition of BMP signaling reduces MMP-2 and MMP-9 expression and obstructs wound healing in regenerating fin of teleost fish Poecilia latipinna

Cited by 20 publications

References 45 publications

Variation in expression and activity pattern ofmmp2andmmp9on different time scales in the regenerating caudal fin ofPoecilia latipinna

Variation in expression and activity pattern ofmmp2andmmp9on different time scales in the regenerating caudal fin ofPoecilia latipinna

Temporal Expression Pattern of Peptides in the Regenerating Caudal Fin of Teleost Fish Poecilia latipinna With Special Emphasis on krt15 and myl-1

Matrix metalloproteinases in bone development and pathology: current knowledge and potential clinical utility

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